Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation (IMPAKT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03076151|
Recruitment Status : Completed
First Posted : March 10, 2017
Last Update Posted : September 6, 2019
Tacrolimus is a calcineurin inhibitor widely used for the prevention of allograft rejection in solid organ and bone marrow transplantation. It is characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Adoport® is an immediate-release formulation of tacrolimus, to be administered twice daily. Because of a narrow therapeutic window and a better correlation between pre-dose level and effects than between dose and effect, therapeutic drug monitoring (TDM) based on trough whole blood tacrolimus concentrations is recommended for Adoport®. TDM helps to minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).
As reported in a consensus document from a consortium of European experts on tacrolimus TDM, the interdose area-under-the curve (AUC0-12h) is expected to be the best marker of tacrolimus exposure. However, tacrolimus monitoring based on full AUC0-12h is difficult to set up in routine, due to clinical constraints and the necessity of multiple samples. Calculation of the AUC0-12h using Bayesian estimation and a limited sampling strategy, i.e. a few blood samples collected during the early phase post-dose would represent an elegant solution, as already done for other tacrolimus formulations.
Furthermore, the pharmacokinetics (PK) of tacrolimus is influenced by a single nucleotide polymorphism within intron 3 of cytochrome P450 3A5 (CYP3A5). Patients who carry at least one CYP3A5*1 allele are considered to be CYP3A5 expressors (about 12% of the Caucasian population, Hapmap project) and thus require a 1.5 to 2-fold higher starting dose than CYP3A5*3/*3 carriers to reach the predefined target exposure early after transplantation. Although this polymorphism showed no impact on the performance of the Bayesian estimators previously developed for other tacrolimus formulation, the patient status for CYP3A5*3 will be considered in this pharmacokinetic study as a potential covariate in, or confounding factor of, the PK model. Specifically, owing to a 12% frequency in the White European population, about 4 patients carriers of the CYP3A5*1 allele are expected in this study; the performance of the PK model and Bayesian estimator developed will be specifically evaluated in this subgroup.
|Condition or disease||Intervention/treatment||Phase|
|Transplantation Kidney Pharmacokinetic||Drug: Tacrolimus monohydrate (ADOPORT®)||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Interventional Multicentre Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation|
|Actual Study Start Date :||February 12, 2018|
|Actual Primary Completion Date :||July 31, 2019|
|Actual Study Completion Date :||July 31, 2019|
Experimental: Tacrolimus monohydrate (ADOPORT®)
patients with de novo Kidney Transplantation under Tacrolimus (ADOPORT®) treatment.
Drug: Tacrolimus monohydrate (ADOPORT®)
Pharmacokinetic of Tracrolimus (ADOPORT®) on 9 blood sampling by kinetics on 4 kinetics
- Tacrolimus bayesian estimator performance [ Time Frame: Month 3 ]The evaluation of Bayesian estimator performance will be based on its capacity to predict tacrolimus AUC (Area Under the Curve), expressed as the bias (%) between the predicted AUC with the PK model and the tacrolimus AUC calculated using the linear trapezoidal rule.
- Tacrolimus concentrations predicted by the PK model using a limited sample strategy [ Time Frame: Month 3 ]The evaluation of the Bayesian estimator performance will be based on its capacity to predict, using a limited number of samples collected during the early phase post-dose, observed tacrolimus AUC0-12h measured using the non-compartmental trapezoidal method with all the time points
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03076151
|Amiens Picardie University Hospital|
|Amiens, France, 80054|
|Limoges University Hospital|
|Limoges, France, 87042|
|Poitiers University Hospital|
|Poitiers, France, 86000|
|CHU de ROUEN|
|Rouen, France, 76013|
|Tours University Hospital|
|Tours, France, 37000|
|Principal Investigator:||Pierre Marquet, MD||University Hospital, Limoges|